A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty
Study Details
Study Description
Brief Summary
This study will evaluate the safety, tolerability and effect of GRF6021 on clinical recovery parameters in patients undergoing primary hip or knee arthroplasty.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a randomized, placebo-controlled, double-blind pilot study to investigate the effects of GRF6021, a 5% human plasma protein fraction administered by intravenous (IV) infusion, on intracellular signaling cascades in blood leukocytes in subjects undergoing primary hip or knee arthroplasty.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GRF6021 Subjects will receive GRF6021 per the following schedule: On the day before surgery On the day of surgery within 4 hours before surgery start (first incision) On the day of surgery upon arrival in the postoperative care unit (within 5 hours after the first incision) On the day after surgery |
Biological: GRF6021
for IV infusion
|
| Placebo Comparator: Placebo Subjects will receive Placebo per the following schedule: On the day before surgery On the day of surgery within 4 hours before surgery start (first incision) On the day of surgery upon arrival in the postoperative care unit (within 5 hours after the first incision) On the day after surgery |
Other: Placebo
for IV infusion
|
Outcome Measures
Primary Outcome Measures
- Intracellular signaling cascades in blood leukocytes [Baseline to Day 3]
Effect of GRF6021 on intracellular signaling cascades in blood leukocytes as determined by CyTOF.
Secondary Outcome Measures
- 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) [Baseline to Day 3]
Change from baseline in 3D-CAM. The 3D-CAM is a verbal assessment tool used to test patients for delirium. Each item in the instrument directly informs acute onset of mental status change or fluctuating course of cognition, inattention, disorganized thinking, and altered level of consciousness.
- Surgery Recovery Scale (SRS) [Baseline to 6 weeks]
Time to 50% recovery of the baseline value in the SRS. The SRS tool assesses functional recovery following major surgery. Impacts on daily activities are scored from 1 to 5 or 6 (1= not at all).
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Pain] [Baseline to 6 weeks]
Time to a score of < 12/40 on a subset of questions from the WOMAC, Pain Subscale. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the Pain subscale is 0-40 . The subscales are used independently and not summed. Higher scores = worse (Higher pain score = more pain; higher function score = more impairment)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Function] [Baseline to 6 weeks]
Time to a score of < 18/60 on a subset of questions from the WOMAC, Physical Function Subscale. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the Function subscale is 0-60 . The subscales are used independently and not summed. Higher scores = worse (Higher pain score = more pain; higher function score = more impairment)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Total] [Baseline to 6 weeks]
The WOMAC total is a sum of scores from the Pain, Stiffness and Function Subscales. The WOMAC assesses pain, stiffness, and physical function in patients with knee and/or hip osteoarthritis. This is an 11-point scale (0-10). The range for the combined subscales is 0-240. (Higher total score = more pain, stiffness, and impairment)
- Short Form Health Survey 36 (SF-36) [Baseline to 6 weeks]
Change from baseline in the SF-36. The SF-36 is a health-related quality-of-life measure, using 8 sub-scale scores and 2 summary scores for mental and physical health. Range: 0-100 Lower = worse Eight subscales vitality physical functioning bodily pain general health perceptions physical role functioning emotional role functioning social role functioning mental health Subscales scores are converted to a z score and given equal weight; max total score is 100
- Beck Depression Inventory-II (BDI-II) [Baseline to 6 weeks]
Change from baseline in the BDI-II. The BDI-II assesses mood in a 21-item self-administered survey. It is scored on a scale of 0-63 in a list of four statements arranged in increasing severity about a particular symptom of depression. Range 0-63 Higher = worse Subscales N/A
- Opioid Analgesic Consumption [Baseline to 6 weeks]
Opioid analgesic consumption during hospital stay and after discharge to end of study.
- Discharge [Baseline to 6 weeks]
Time to discharge.
- Perioperative outcomes [Blood] [Baseline to Day 2]
Intraoperative blood products (mL)
- Perioperative outcomes [Fluids] [Baseline to Day 2]
Intraoperative fluids (mL)
- Functional status using the ActiGraph [Baseline to 6 weeks]
Change in functional status using the ActiGraph wearable device providing measurements for physical activity, mobility, and sleep.
- Vital sign measurements [BP] [Baseline to Day 3]
Change from baseline in vital sign measurements: Blood pressure (mm Hg)
- Vital sign measurements [Heart] [Baseline to Day 3]
Change from baseline in vital sign measurements: Heart rate (bpm)
- Electrocardiogram (ECG) [Rate] [Baseline to Day 3]
Change from baseline in ECG: Rate (bpm)
- Electrocardiogram (ECG) [Rhythm] [Baseline to Day 3]
Change from baseline in ECG: Rhythm (sinus or non-sinus)
- Electrocardiogram (ECG) [QT] [Baseline to Day 3]
Change from baseline in ECG: QT interval (ms)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men and women 50-85 years of age scheduled to undergo primary total hip or knee replacement surgery.
-
Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 .
Exclusion Criteria:
-
Blood coagulation disorders.
-
Subjects who started chronic anticoagulant therapy (warfarin, heparin, low-molecular weight heparin, or Factor Xa inhibitors) in the last 6 months
-
Hypercoagulable state.
-
Prior hypersensitivity to any human blood product including plasma.
-
Treatment with any human blood product, including transfusions and IV immunoglobulin, during the 6 months prior to screening.
-
History of immunoglobulin A or haptoglobin deficiency.
-
Major surgery, trauma or injury in the last 3 months or minor surgery in the last 1 month.
-
Heart disease or congestive heart failure in the 6 months prior to dosing.
-
Poorly controlled hypertension.
-
Severe anemia.
-
Functional impairment of major joint or lower extremity other than joint undergoing surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University Medical Center | Palo Alto | California | United States | 94305 |
Sponsors and Collaborators
- Alkahest, Inc.
Investigators
- Study Director: Alkahest Medical Monitor, Alkahest, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AKST6021-211